Project Summary The effects of rising environmental temperatures on heat-related illnesses (HRI) are of increasing concern, particularly for vulnerable subgroups of the US population who work strenuously in hot environments, with HRI emerging as a serious threat to public health. The average annual rates of heat-related death in construction workers is surpassed only by those in agricultural workers, and Latino construction workers have the highest on-the job morbidity and all-cause mortality of any ethnic group working in construction. Routine work in these high heat and high exertion occupational settings without adequate HRI prevention measures may challenge the body's capacity to adapt and may lead to more rapid progression down the HRI cascade, ranging from heat cramps to multi-organ failure in extreme cases. The goal of this work is 1) obtain advanced skills and expertise in metabolomics and big data analytics; and 2) utilize established physiologic biomonitoring protocols in a new group of vulnerable workers with the addition of metabolomics and expanded biomarker analysis. This work will set the foundation for a larger in-depth study aimed to more fully understand the physiologic drivers of heat related illness and its complications at the metabolic level in this population. Establishing the methodology for preliminary identification of candidate metabolites of typical physiologic pathways activated in the heat stress response, and biomarkers of interest that are associated with metabolomic profiles will be paramount for considering the physiologic drivers of heat-related morbidity and mortality, and eventually, interactions between heat and other exposures and heat-related exacerbation of chronic disease. Future, larger studies based on this foundational work will characterize the metabolomic pathways of the physiologic response to heat in a broader occupational sample, which will allow for documentation of the physiologic impacts of future heat- adaptive interventions for vulnerable worker populations.